Craniofacial Shape Variation in <i>Twist1^+/−</i> Mutant Mice

<jats:title>ABSTRACT</jats:title><jats:p>Craniosynostosis (CS) is a relatively common birth defect resulting from the premature fusion of one or more cranial sutures. Human genetic studies have identified several genes in association with CS. One such gene that has been implicated in both syndromic (Saethre–Chotzen syndrome) and nonsyndromic forms of CS in humans is <jats:italic>TWIST1</jats:italic>. In this study, a heterozygous <jats:italic>Twist1</jats:italic> knock out (<jats:italic>Twist1<jats:sup>+/−</jats:sup></jats:italic>) mouse model was used to study the craniofacial shape changes associated with the partial loss of function. A geometric morphometric approach was used to analyze landmark data derived from microcomputed tomography scans to compare craniofacial shape between 17 <jats:italic>Twist1<jats:sup>+/−</jats:sup></jats:italic> mice and 26 of their <jats:italic>Twist1</jats:italic><jats:sup>+/+</jats:sup> (wild type) littermate controls at 15 days of age. The results show that despite the purported wide variation in synostotic severity, <jats:italic>Twist1<jats:sup>+/−</jats:sup></jats:italic> mice have a consistent pattern of craniofacial dysmorphology affecting all major regions of the skull. Similar to Saethre–Chotzen, the calvarium is acrocephalic and wide with an overall brachycephalic shape. Mutant mice also exhibited a shortened cranial base and a wider and shorted face, consistent with coronal CS associated phenotypes. The results suggest that these differences are at least partially the direct result of the <jats:italic>Twist1</jats:italic> haploinsufficiency on the developing craniofacial skeleton. This study provides a quantitative phenotype complement to the developmental and molecular genetic research previously done on <jats:italic>Twist1</jats:italic>. These results can be used to generate further hypotheses about the effect of <jats:italic>Twist1</jats:italic> and premature suture fusion on the entire craniofacial skeleton. Anat Rec, 297:826–833, 2014. © 2014 Wiley Periodicals, Inc.</jats:p>